A phase II trial of EMD72000 (matuzumab), a humanized anti-EGFR monoclonal antibody, in patients with platinum-resistant ovarian and primary peritoneal malignancies

Seiden, Michael V.; Burris, Howard A.; Matulonis, Ursula A.; Hall, James B.; Armstrong, Deborah K.; Speyer, James L.; Weber, J; Fm, Muggia

doi:10.1016/j.ygyno.2006.10.019

Cited by 117 publications

(54 citation statements)

References 35 publications

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“…This has been demonstrated in both ovarian and colorectal cancers (12,52). Clinical trials performed using an EGFR monoclonal antibody for the treatment of receptor-positive cancers did not demonstrate clinical efficacy as a monoclonal antibody therapy, further illustrating the difficulty of predicting antibody responses based on overexpression alone (53). However, the positive LAMP-1 signal might be predictive of a specific ovarian cancer modality and might assist in treatment in EGFR-positive serous ovarian malignancies.…”

Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Temporally Stimulated Ovarian Cancer Cells for Biomarker Discovery

Marzinke

Choi

Chen

et al. 2013

Molecular & Cellular Proteomics

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While ovarian cancer remains the most lethal gynecological malignancy in the United States, there are no biomarkers available that are able to predict therapeutic responses to ovarian malignancies. One major hurdle in the identification of useful biomarkers has been the ability to obtain enough ovarian cancer cells from primary tissues diagnosed in the early stages of serous carcinomas, the most deadly subtype of ovarian tumor. In order to detect ovarian cancer in a state of hyperproliferation, we analyzed the implications of molecular signaling cascades in the ovarian cancer cell line OVCAR3 in a temporal manner, using a mass-spectrometry-based proteomics approach. OVCAR3 cells were treated with EGF 1 , and the time course of cell progression was monitored based on Akt phosphorylation and growth dynamics. EGF-stimulated Akt phosphorylation was detected at 12 h posttreatment, but an effect on proliferation was not observed until 48 h post-exposure. Growth-stimulated cellular lysates were analyzed for protein profiles between treatment groups and across time points using iTRAQ labeling and mass spectrometry. The protein response to EGF treatment was identified via iTRAQ analysis in EGF-stimulated lysates relative to vehicle-treated specimens across the treatment time course. Validation studies were performed on one of the differentially regulated proteins, lysosomal-associated membrane protein 1 (LAMP-1), in human tissue lysates and ovarian tumor tissue sections. Further, tissue microarray analysis was performed to demarcate LAMP-1 expression across different stages of epithelial ovarian cancers. These data support the use of this approach for the efficient identification of tissuebased markers in tumor development related to specific signaling pathways. LAMP-1 is a promising biomarker for studies of the progression of EGF-stimulated ovarian cancers and might be useful in predicting treatment responses involving tyrosine kinase inhibitors or EGF receptor monoclonal antibodies. Molecular & Cellular

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Section: Discussionmentioning

confidence: 99%

Proteomic Analysis of Temporally Stimulated Ovarian Cancer Cells for Biomarker Discovery

Marzinke

Choi

Chen

et al. 2013

Molecular & Cellular Proteomics

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“…In clinical studies prolonged treatment with cetuximab or matuzumab has generally been well tolerated, with skin reactions such as an acne-like rash being the most common side effect (Baselga et al, 2005;Rao et al, 2008;Seiden et al, 2007). Furthermore, endogenous humoral and cellular anti-EGFR immune responses have been observed in cancer patients (Shomura et al, 2004), suggesting that limited autoimmunity to EGFR is acceptable.…”

Section: Discussionmentioning

confidence: 99%

Peptide mimotopes recognized by antibodies cetuximab and matuzumab induce a functionally equivalent anti-EGFR immune response

et al. 2010

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“…A small phase II trial designed on platinum-refractory/resistant EGFR positive setting on cetuximab as single agent demonstrated marginal benefit in term of PFS [69]. Matuzumab, a humanized anti-EGFR monoclonal antibody, in patients heavily pretreated, did not show activity in this setting [70].…”

Section: The Involvement Of Her-pathway In Platinum-resistancementioning

confidence: 99%

Target Therapy in Platinum-Refractory/Resistant Ovarian Cancer: From Preclinical Findings to Current Clinical Practice

Staropoli¹,

Botta²,

Ciliberto³

et al. 2013

JCT

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Epithelial ovarian cancer (EOC) is the sixth most common malignancy in women. Ovarian tumors consist of several clinical and pathological entities that share an anatomic site. The gold standard treatment, both in front-line and in adjuvant setting, is represented by carboplatin/paclitaxel combination. Conversely, the second-line treatment is not well defined. The response to platinum is the major prognostic factor for survival. In this review we discuss the current views on platinum-refractory/resistant patient treatment only, which includes patients progressing or relapsing within 6 months from the last platinum-based course. Concerning this subgroup, the activity of several conventional drugs was confirmed in different trials without a significant impact in terms of overall survival. In the last years particular emphasis was given to targeted anti-angiogenetic therapy which produced a survival improvement with an acceptable toxicity profile. New "ad hoc" approaches, with a major attention to outcome-predictive factors, are eagerly awaited.

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A phase II trial of EMD72000 (matuzumab), a humanized anti-EGFR monoclonal antibody, in patients with platinum-resistant ovarian and primary peritoneal malignancies

Cited by 117 publications

References 35 publications

Proteomic Analysis of Temporally Stimulated Ovarian Cancer Cells for Biomarker Discovery

Proteomic Analysis of Temporally Stimulated Ovarian Cancer Cells for Biomarker Discovery

Peptide mimotopes recognized by antibodies cetuximab and matuzumab induce a functionally equivalent anti-EGFR immune response

Target Therapy in Platinum-Refractory/Resistant Ovarian Cancer: From Preclinical Findings to Current Clinical Practice

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